CLONING OF THE LAMININ ALPHA-3 CHAIN GENE (LAMA3) AND IDENTIFICATION OF A HOMOZYGOUS DELETION IN A PATIENT WITH HERLITZ JUNCTIONAL EPIDERMOLYSIS-BULLOSA
F. Vidal et al., CLONING OF THE LAMININ ALPHA-3 CHAIN GENE (LAMA3) AND IDENTIFICATION OF A HOMOZYGOUS DELETION IN A PATIENT WITH HERLITZ JUNCTIONAL EPIDERMOLYSIS-BULLOSA, Genomics, 30(2), 1995, pp. 273-280
Laminin 5 and laminin 6 are basement membrane proteins synthesized by
the basal cells of stratifying squamous epithelia. Altered expression
of laminin 5 has been associated with Herlitz junctional epidermolysis
bullosa (H-JEB), a severe epidermal blistering disorder inherited as
an autosomal recessive disease. We have isolated cDNA clones encoding
the alpha 3 chain of laminin 5 and searched for mutations in the LAMA3
gene in H-JEB patients. In one H-JEB family, an affected individual e
xhibited drastically reduced immunoreactivity to antibodies directed a
gainst the alpha 3 chain of laminin 5 and an impaired expression of th
e corresponding mRNA transcripts. RT-PCR analysis of mRNA extracted fr
om the proband's keratinocytes identified a homozygous single basepair
deletion in the transcripts encoding the laminin alpha 3A and alpha 3
B isoforms. The mutation causes a frameshift and premature termination
codon in both alleles of the LAMA3 gene. Inheritance of the clinical
H-JEB phenotype was consistent with the segregation of the mutated all
ele in the family. We also report the identity of the alpha chains of
laminin 5 and epiligrin and provide evidence that LAMA3 transcripts ar
e distinct from the laminin 6 alpha chain mRNA. (C) 1995 Academic Pres
s, Inc.